Association of microRNA-652 Expression with Radiation Response of Colorectal Cancer: A Study from Rectal Cancer Patients in a Swedish Trial of Preoperative Radiotherapy to Public Data Analysis and in Vitro Investigation

Purpose: Radiotherapy (RT) is a standard adjuvant therapy in progressive rectal cancer patients, but many patients are resistant to RT, leading to poor prognosis. Our study identified microRNA-652 (miR-652) value on RT response and outcome in rectal cancer patients.Methods: miR-652 expression was determined by RT-PCR in primary rectal cancer from 48 patients with and 53 patients without RT. The relationship of miR-652 with biological factors and prognosis were examined. The biological function of miR-652 was identified through TCGA and GEPIA database search. Two human colon cancer cell lines (HCT116 p53+/+ and p53-/-) were used for in vitro study. Results: miR-652 expression was augmented significantly in cancer than normal mucosa in non-RT patients (P=0.044). High miR-652 expression in non-RT patients was related to more apoptosis (P=0.036), ATM (P=0.010) and DNp73 expression (P=0.009). High miR-652 expression was related to worse disease-free survival of non-RT patients, independent of gender, age, tumor stage and differentiation (P=0.028; HR=7.398, 95% CI 0.217-3.786). The biological functional analysis further identified the prognostic value and potential relationship of miR-652 with the apoptosis in rectal cancer. In RT patients, miR-652 expression was notably decreased in cancers when compared to non-RT cases (P=0.047), and miR-652 expression in cancers was negatively related to WRAP53 expression (P=0.022). After miR-652 inhibition, the estimation of reactive oxygen species, caspase activity and apoptosis in HCT116 p53+/+ cells were significantly increased compared with HCT116 p53-/- cells after radiation.Conclusions Our findings suggest the potential value of miR-652 expression as a marker for the prediction of radiation response and clinical outcome in rectal cancer patients.